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However, its specific role in tumor angiogenesis has remained unexplored. Here, we identify endothelial Epac1 as a critical driver of melanoma angiogenesis. Analysis of patient-derived melanomas revealed that Epac1 is markedly upregulated in tumor endothelial cells. Using both global and endothelial-specific\n                    <jats:italic>Epac1<\/jats:italic>\n                    knockout mouse models, we demonstrate that\n                    <jats:italic>Epac1<\/jats:italic>\n                    deletion reduced melanoma growth and vascularization following subcutaneous melanoma cell inoculation. Transcriptome profiling of tumor-associated endothelial cells from\n                    <jats:italic>Epac1<\/jats:italic>\n                    -deficient mice showed broad downregulation of pro-angiogenic and YAP\/TAZ target genes. This was corroborated in vitro using an\n                    <jats:italic>Epac1<\/jats:italic>\n                    knockout endothelial cell line, where VEGFR2 expression, YAP\/TAZ nuclear translocation, and YAP\/TAZ target gene transcription were all suppressed. Consistently,\n                    <jats:italic>Epac1<\/jats:italic>\n                    deletion impaired VE-cadherin\/VEGFR2 interaction, VEGF-dependent nuclear YAP\/TAZ and transcriptional activity, and abolished endothelial cell alignment in response to shear stress. Collectively, our results reveal Epac1 as a central modulator of VEGFR2 and YAP\/TAZ signalling, integrating angiogenic and mechanosensory cues during melanoma vascularization.\n                  <\/jats:p>","DOI":"10.1007\/s10456-026-10080-6","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:56:47Z","timestamp":1790168207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial Epac1 facilitates YAP\/TAZ controlled melanoma growth and angiogenesis"],"prefix":"10.1007","volume":"29","author":[{"given":"Yohanes Cakrapradipta","family":"Wibowo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Cordero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Levay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Ola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergana","family":"Dobreva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Langer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Vettel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepp","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"10080_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ceb.2011.10.002","volume":"23","author":"A Wacker","year":"2011","unstructured":"Wacker A, Gerhardt H (2011) Endothelial development taking shape. 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